Aim: The purpose of the study is to verify if there is statistic difference of lung function before surgery based on differences in clinical characteristics (sex, age, degree of differentiation, size of tumor, tumor node metastasis (TNM), methods of surgeries, pleural metastasis, and lymph gland metastasis). Another purpose is to test if forced expiratory volume in 1 s/forced vital capacity obstruction (FEV1/FVC) is a risk factor of the prognosis of lung cancer. Methods: This retrospective study used t-test or analysis of variance to explore whether dramatic difference of lung function (FVC, FEV1, maximal voluntary ventilation [MVV], and FEV1/FVC) existed based on differences in clinical characteristics. The study used the Kaplan–Meier method to verify if FEV1/FVC could be a risk factor to predict the prognosis of lung cancer patients after surgeries. Results: The statistical results indicated that statistical difference of FVC existed between different age groups. In patients of different ages and sexes, there was statistically different MVV. Results of FEV1/FVC showed that FEV1/FVC varied dramatically in patients of different pleural metastasis conditions or TNM. Analysis of prognosis proved that in patients with a different differentiation degree, size of tumor, metastasis conditions of lymph gland, and TNM stage, a statistically different prognosis was found. As for groups of normal and abnormal FEV1/FVC, no apparently different prognosis was observed. Analysis of lung cancer patients of stage I indicated that the 5-year survival was dramatically different between patients of normal and abnormal FEV1/FVC. Conclusion: In lung cancer patients of stage I, FEV1/FVC was one of the risk factors of prognosis.

A relatively high morbidity exists in lung cancer.[1],[2],[3] The morbidity of lung cancer in men was the highest among all kinds of cancers, and it is also high in women.[4],[5],[6] Thus, estimating prognosis of lung cancer is important. Currently, the main factors for predicting the prognosis are pathological type, tumor node metastasis stage (TNM), metastasis, and tumor markers.[7],[8] Pulmonary function is an important factor affecting the safety of surgeries, so it is possible that pulmonary function can also estimate the prognosis of lung cancer.

Clinically, vital capacity (VC), total lung capacity, maximal voluntary ventilation (MVV), FVC, FEV1, FEV1/FVC, and peak expiratory flow (PEF) are commonly used to evaluate pulmonary function.[9],[10] Considering feasibility, FVC, FEV1, MVV, and FEV1/FVC were chosen in this study. FVC is all the amount of air, after deep inhalation, with full power and speed. FEV1 is the amount of air in the first second, after deep inhalation. MVV is the amount of air within 1 min, with full power and speed.

Recently, FVC, FEV1, and MVV have been widely used clinically, and their relationship with prognosis of lung cancer has been reported.[11] It has been reported that FVC and FEV1 decreased dramatically after lung cancer surgery.[12] Some papers have indicated that pulmonary function could affect outcomes of nonsmall cell lung cancer (NSCLC), and FVC could be an independent risk factor affecting prognosis of NSCLC.[13],[14]

The study by Launo et al.[15] showed that low MVV could increase the morbidity, mortality, and operative risk. However, the concept that FEV1 could be an independent risk factor of outcomes is controversial. Lin et al.[13] indicated that FEV1 could be an independent risk factor of prognosis, but FEV1 before surgeries could not be used to evaluate the outcomes in study carried out by Guo and Du.[14]

In summary, it is possible that pulmonary function can be used to evaluate outcomes of lung cancer. However the relationship between FEV1/FVC and outcomes remains unclear. Besides, it is controversial that patients with different clinical characters have statistically different pulmonary function such as FVC, FEV1, MVV, and FEV1/FVC.

In our study, data on 248 patients with a diagnosis of lung cancer by surgery or pathology were collected. This was a retrospective study. Data were analyzed statistically to verify whether patients with different clinical characteristics (sex, age, degree of differentiation, size of tumor, TNM, methods of surgeries, pleural metastasis, and lymph gland metastasis) had statistically different pulmonary function. Another purpose of the study was to test whether decrease of FEV1/FVC can be used to evaluate outcomes of patients in stage I lung cancer.

Methods

Clinical data

We collected lung cancer cases after surgery in the Department of Thoracic Surgery, First Affiliated Hospital of Dalian Medical University from January 2008 to December 2013. In total, 248 patients were included in the study. All the cases were diagnosed with lung cancer pathologically. The data after surgery were obtained by telephone or outpatient service. Basic data such as sex, age, degree of differentiation, the size of tumor, TNM stages, methods of surgeries, pleural metastasis, lymph gland metastasis, FVC, FEV1, MVV, FEV1/FVC, and 5-year survival of all patients were collected.

This retrospective study used t-test or analysis of variance to explore whether statistically significant difference of lung function (FVC, FEV1, MVV, and FEV1/FVC) existed in patients whose clinical characters (sex, age, degree of differentiation, size of tumor, TNM stage, methods of surgeries, pleural metastasis, and lymph gland metastasis) were different. The study used the Kaplan–Meier method to verify if decrease of FEV1/FVC could be a risk factor used to predict the prognosis of lung cancer patients after surgeries. The survival curve was calculated by SPSS. In the study, FEV1/FVC lower than 70% was considered to be abnormal. In the study, SPSS 20.0 (IBM, Armonk, New York, USA) was used to analyze the data. When P < 0.05, the difference was considered statistically significant.

In [Table 1], the analysis of clinical characteristics and lung function indicated that there was a statistically significant difference of FVC between different age groups (≤62 and >62, P = 0.049). In this study, the median of age was 62. FVC of the age group ≤ 62 was 84.44% ± 13.49%, and FVC of another group was 81.04% ± 13.24%.{Table 1}

In [Table 2], in patients of different ages and sexes, statistically different MVV was found (P < 0.001, P = 0.003). MVV of men was 84.71 ± 19.36 while MVV of women was 92.92 ± 22.63. MVV of the age group ≤ 62 was 96.64 ± 21.50 while MVV of another group was 81.97 ± 19.22. Results of FEV1/FVC showed that a statistically significant difference of FEV1/FVC was observed in patients of different pleural metastasis conditions or TNM (P = 0.002, P = 0.01).{Table 2}

[Figure 1] shows the survival curve of patients with normal and abnormal FEV1/FVC. No statistically significant difference in 5-year survival was found between normal and abnormal FEV1/FVC (P = 0.299). In [Figure 1], horizontal axis is time, and vertical axis is survival rate. Five-year survival of patients with normal FEV1/FVC was 70.3% while that of patients with abnormal FEV1/FVC was 55.9%.{Figure 1}

In [Table 3], analysis of prognosis showed that in patients with different differentiation degree, size of tumor, metastasis conditions of lymph glands, and TNM stage, a statistically significant different prognosis was found after surgeries (P = 0.006, P = 0.002, P = 0.004, and P = 0.016). [Figure 2] is the survival curve of patients with different TNM stages. Five-year survival of stage I, II, and III was 82.3%, 60.4%, and 33.7%, respectively.{Table 3}{Figure 2}

Analysis of patients with stage I lung cancer indicated that statistically significant difference in outcomes was observed between patients with normal and abnormal FEV1/FVC (P = 0.024). The 5-year survival of patients with normal FEV1/FVC was 94.1% while that of those with abnormal FEV1/FVC was 74.8%. [Figure 3] is the survival curve of normal and abnormal FEV1/FVC in 75 patients with stage I lung cancer.{Figure 3}

Discussion

Currently, lung cancer has become the carcinoma of highest mortality, and the surgery is still an important method of treatment.[16],[17] TNM stage has been the most common method of evaluating prognosis, but it has intrinsic limitations.[18] Hwang et al.[19] indicated that inhospital mortality of lung cancer did not relate to sex, age, and performance status but to severity of organ failure.[19] FVC, FEV1, and FEV1/FVC were effective methods of measuring pulmonary function.[20] Ge et al.[21] reported that, VC, FEV1, FVC, PEF, PEF%, and MVV correlated with outcomes of advanced lung cancer. Of all the pulmonary function indices, FEV1 was the most significant index evaluating surgery's risk. Magdeleinat et al.[22] indicated that if FEV1 or FEV1/FVC was below 50%, there would be 8.5% mortality or 70% complication.

As lung cancer has a very high incidence of mortality, evaluating prognosis evaluating prognosis is significant. Pulmonary function is very important in evaluating the risk of surgery, so we assumed that pulmonary function could be used to evaluate the prognosis of lung cancer. The relationship of FVC, FEV1, MVV, and outcomes has been reported. However, FEV1/FVC was chosen in this study. Two hundred and forty-eight lung cancer cases were collected in this retrospective study to explore whether lung function (FVC, FEV1, MVV, and FEV1/FVC) had statistical difference in patients with different clinical characteristics. The study used the Kaplan–Meier Method to test if FEV1/FVC could be a risk factor to foresee the prognosis of lung cancer patients after surgeries.

Our data showed that statistically different FVC was found in patients of different age groups. Patients of different ages and sexes had statistically significant different MVV. Results of FEV1/FVC show that a statistically significant difference of FEV1/FVC was found among patients with different pleural metastasis conditions or TNM. Interestingly, degree of differentiation, size of tumor, and lymph metastasis are the indexes reflecting cancer progression, but statistically significant difference of FEV1/FVC did not exist. We assumed that these indexes were single ones which could not reflect the whole picture of patients.

Data about 5-year survival showed that patients with different differentiation degree, size of tumor, metastasis conditions of lymph gland, and TNM stage had statistically significant different outcomes after surgeries. However, no statistically significant difference of outcome was observed between normal and abnormal FEV1/FVC. The reason needs to be studied in the coming research.

To explore the relation of outcome and FEV1/FVC, 75 patients with stage I lung cancer were chosen. In stage II or III patients, number of normal FEV1/FVC is too small. Analysis of stage I lung cancer patients indicates that statistically significant difference of 5-year survivals existed between patients with normal and abnormal FEV1/FVC. In patients of all stages, FEV1/FVC did not affect outcomes, while in patients of stage I, it did. We believe that results in stage I were reliable and results of all stages need to be explored in the future.

The main innovation part of this study was the exploration of the relation of FEV1/FVC and outcomes in lung cancer. Because of certain statistical problems, in the study, the relation between FEV1/FVC of patients of stage II or III and outcome could not be researched. Further studies with larger samples are needed to address the aforementioned problem.